Drug Interaction Report

MONITOR: Coadministration of entecavir with another drug that is also eliminated by active tubular secretion may result in increased plasma concentrations of one or both drugs due to competitive inhibition of transporters in the renal tubules. Drugs (and/or their metabolites) that are thought to undergo active tubular secretion include acyclovir, allopurinol, aminosalicylic acid, cidofovir, cimetidine, creatine, dyphylline, famciclovir, famotidine, flecainide, ganciclovir, levetiracetam, metformin, methotrexate, midodrine, mycophenolic acid, oseltamivir, pralatrexate, probenecid, procainamide, quinidine, ranitidine, tenofovir, triamterene, trimethoprim, valacyclovir, valganciclovir, zalcitabine, zidovudine, and many of the beta-lactam and quinolone antibiotics.

MANAGEMENT: Patients receiving entecavir with another drug that undergoes active tubular secretion should be monitored for excessive pharmacologic effects of both drugs, and the dosages adjusted as necessary.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of cefditoren pivoxil. According to the manufacturer, administration of cefditoren pivoxil following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 50% and 70%, respectively, compared to administration in the fasting state. The absolute bioavailability of cefditoren pivoxil is approximately 14% under fasting conditions and 16% when given with a low-fat meal.

MANAGEMENT: To ensure maximal oral absorption, cefditoren pivoxil should be administered with or immediately after a meal.

ADJUST DOSING INTERVAL: Food delays the oral absorption and reduces the oral bioavailability of entecavir. According to the product labeling, administration of entecavir 0.5 mg with a standard high-fat meal or a light meal resulted in a delay in absorption by 0.25 to 0.75 hours, a decrease in the peak plasma concentration (Cmax) by 44% to 46%, and a decrease in the area under the plasma concentration-time curve (AUC) by 18% to 20% compared to administration in the fasting state.

MANAGEMENT: To ensure maximal oral absorption, entecavir should be administered on an empty stomach at least 2 hours after a meal and 2 hours before the next meal.